Razpis: Prevention Beyond the Pipeline
Funding to support prevention drug discovery in relation to Alzheimer's disease, with a focus on areas and approaches which are not currently covered by ADDF and other funders.
Financer: Alzheimer's Drug Discovery Foundation
Največja vrednost projekta: 1.500.000,00 EUR za klinične študije, 150.000,00 - 600.000,00 za predklinične, 50.000,00 - 100.000,00 za epidemiološke analize
Upravičenost kandidatov: javne in zasebne pravne osebe, profitne in neprofitne organizacije, vključno z akademskimi ustanovami in biotehnološkimi podjetji, ne glede na lokacijo
Rok za prijavo: 17. 11. 2017
Prijava: preko portala za prijavo
Founded in 1998 by co-chairman Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation (ADDF) provides funding to leading scientists who are conducting the most promising and innovative Alzheimer's drug research worldwide.
The ADDF aims to plug the translational funding gap between basic research and later stage drug development by funding promising preclinical drug discovery and biomarker development programmes relevant to Alzheimer's diseas, other dementias and cognitive ageing.
The ADDF's Prevention Beyond the Pipeline programme seeks to support Alzheimer's prevention drug discovery not covered by most research funders or current ADDF requests for proposals. ADDF's current priority areas for prevention drug research are:
- Consortium or Cohorts for Alzheimer's Prevention Action (CAPA) - Much information on how the risk of dementia or cognitive decline may be influenced by long-term exposure to specific foods, supplements, and drugs has been provided by recent epidemiological studies. Following this work, new studies are needed to provide researchers with information on dose, duration, and responder profiles, so that the epidemiological research can translate into actionable interventions for testing.
- Comparative Effectiveness Research - When treating certain health conditions, physicians may sometimes have a choice of clinically equivalent drugs. Some of these drugs may have the potential treat Alzheimer's owing to disease-modifying properties other than those being used to treat the disease for which they are currently used. The ADDF aims to fund research on whether clinical treatment of pre-existing conditions could, by opting to employ drugs with properties relevant to the prevention of Alzheimer's, protect against the future development of dementia. Priority will be given to the comparison of drugs that are otherwise clinically equivalent for the pre-existing condition. Methods may include randomised clinical trials, epidemiology, and preclinical research.
- Cognitive Decline and Cognitive Reserve - Ageing and health conditions associated with cognitive decline are linked to and increased risk of dementia. The ADDF will consider funding drug discovery programs to prevent and treat these conditions, including cognitive ageing, postoperative delirium and postoperative cognitive decline, mild and/or repetitive traumatic brain injury, and chemotherapy-induced decline. Methods may include clinical trials, epidemiology, or preclinical research.
ADDF grants are generally awarded for periods of one to two years, with the potential for further funding contingent on the meeting of agreed targets. Where the proposed undertaking justifies a longer research timeframe, multi-year proposals may be considered.
Budgets must be justified by the scientific work plan.
The following costs are not covered:
- Indirect costs/overheads
- Capital equipment
- Equipment service contracts
- Publication costs
- Travel (unless travel is pre-approved under speical circumstances)
Terms and Conditions
Full proposals will be reviewed by ADDF scientific staff and at least two members of the ADDF Scientific Review Board. The reviewers will evaluate proposals based on the following criteria:
For Preclinical Studies:
- Biological "Druability":
- Description of the target including any structural or computational biology known about the target (e.g. X-ray structure, binding site prediction, domain analysis, sequence comparisons).
- Systems biology analysis - Has the systems biology of the target been assessed? Is the target a node, or is there likely high possibility for redundancy?
- Availability of biological assays and description of duration and throughput - How do there assays translate in vivo, and in the context of the disease in humans?
- Potential mechanism-related side effects in animals and humans linked to modulating this target - What are the potential safety considerations due to likely off target activities or on peripheral targets?
- Related programmes in the field; if any are known, applicants should explain the advantages of their programme.
- Chemical "Drugability":
- Chemical propertis of the compound(s) to allow for assessment of "drugability" - All information provided is kept under strict confidentiality. All reviewers and ADDF staff are required to sign Confidentiality Disclosure Agreements (CDA).
- The starting point of compound/compound series description, eg natural compound, commerically available compound, virtual screen, proprietary drug like lead, existing FDA approved drug.
- Available compounds with similar mechanism of action - Where appropriate, it is recommended that comparistion studies be included.
- Range of activity in primary, seconday and cellular assays.
- In vivo Proof-of-Concept/Efficacy studies:
- Justification for in vivo studies - The project plan or supporting data should include medicinal chemistry refinement, preliminary ADMET studies and PK/PD studies and/or dose finding studies to justify moving into in vivo studies. A discussion or evidence for blood-brain barrier permeability, dose optimisation, and details for expected route of administration should also be included.
- PK studies - While not required to be as comprehensive as IND-enabling studies, PK studies are required to demonstrate with enough confidence that the drug will reach the target sufficient concentrations to mediate an effect.
For Clinical and Biomarker Studies:
- Clear justification for the proposed clinical study including discussion of supporting preclinical in vivo data.
- Clear definition of the control/placebo to be used and discussion regarding ethical considerations.
- Studies with patients or patient-derived material - The patient population should be clearly defined including detailed inclusion/exclusion criteria.
- Demonstration of power analysis to define numbers of patients or samples - Provide appropriate statistical reasoning to justify the proposed sample size and whether this will allow for adequate testing of the hypothesis.
- Recruitment issues - Include discussion that supports recruitment for the proposed trial. Investigators should be cognizant of recruitment difficulties in mild cognitive impairment (MCI) populations and provide evidence for ability to recruit the proposed patient population and number.
- Validation of biomarkers (within the literature or pilot studies) to detect changes in defined patient population within the specified treatment time of the proposed trial.
- Full IRB-ready protocol - Protocal for submission to the IRB should be included even if IRB approval has not yet been sought or awarded.
- Future plans for regulatory strategy and approval, where appropriate, ie feasibility of manufacture, intellectual property.
- Critical next experiments in order to advance the programme to attract additional funding/licensing.
Teams and Resources: Interdisciplinary teams across the fields of biology, medicinal chemistry, bioinformatics, pharmacology, toxicology, regulatory, intellectual property and clinical development are higly valued. The following will be considered when reviewing the investigative team and resources:
- Does the investigative team have access to the required expertise and resources required to conduct the study, eg if a compound modification/optimisation plan is proposed, do sufficient medicinal chemistry and pharmacokinetics capabilities exist within the investigative team and/or related contractors to support the project?
- Has the applicant consulted with individuals with drug/clinical development expertise for the development of a commercialisation plan? Where appropriate, have these individuals been consulted during desing of the early preclinical studies?
- Where internal expertise is not available, has the applicant identifies external partners e.g. consultants, contract research organisations (CROs) for execution of the experimental plan?